| Title: |
FRAME: A phase I trial of defactinib (FAK inhibitor) in combination with avutometinib (RAF-MEK clamp) in patients with solid tumours including low grade serous ovarian cancer |
| Authors: |
Banerji, Udai; Banerjee, Susana; Krebs, Matthew; Greystoke, Alastair; Garces, Alvaro Inglese; Perez, Vicky Sanchez; Terbuch, Angelika; Shinde, Rajiv; Caldwell, Reece; Grochot, Rafael; Ruddle, Ruth; Gurel, Bora; Swales, Karen; Tunariu, Nina; Prout, Toby; Parmar, Mona; Symeonides, Stefan; Rekowski, Jan; Yap, Christina; Sharp, Adam; Paschalis, Alec; Lopez, Juanita; Minchom, Anna; Bono, Johann |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2024 |
| Description: |
We describe the first-in-human trial of avutometinib (RAF/MEK clamp) and defactinib (FAK inhibitor) in patients with solid tumors. The trial met its primary endpoint and recommended a phase 2 dose/schedule is avutometinib 3.2 mg OD 2/7 days and defactinib 200 mg BID 7/7 days, both drugs administered orally for 3 weeks every 4 weeks. The pharmacokinetics and pharmacodynamics were consistent with previous reports of avutometinib and defactinib used as single agents. Key findings include an objective response rate (ORR) and median progression free survival (mPFS) of 42.3% (11/26; 95% confidence interval (CI): 23.4%-63.1%) and 20.1 months (95% CI: 11.2-43.9) respectively in patients with low grade serous ovarian cancer (LGSOC). This study demonstrates importance of novel combinations of targeted therapies targeting the MAPK and FAK involving intermittent dosing schedules to improve tolerability (NCT03875820/EudraCT number 2017-001035-39). |
| Document Type: |
other/unknown material |
| Language: |
unknown |
| DOI: |
10.21203/rs.3.rs-5632942/v1 |
| Availability: |
https://doi.org/10.21203/rs.3.rs-5632942/v1; https://www.researchsquare.com/article/rs-5632942/v1; https://www.researchsquare.com/article/rs-5632942/v1.html |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.698D3093 |
| Database: |
BASE |